*Review* **The Maze Pathway of Coevolution: A Critical Review over the** *Leishmania* **and Its Endosymbiotic History**

**Lilian Motta Cantanhêde , Carlos Mata-Somarribas, Khaled Chourabi, Gabriela Pereira da Silva, Bruna Dias das Chagas, Luiza de Oliveira R. Pereira , Mariana Côrtes Boité and Elisa Cupolillo \***

> Research on Leishmaniasis Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040360, Brazil; lilian.cantanhede@ioc.fiocruz.br (L.M.C.); carlos.somarribas@ioc.fiocruz.br (C.M.-S.);

khaled.chourabi@ioc.fiocruz.br (K.C.); gabriela.silva@ioc.fiocruz.br (G.P.d.S.);

bruna.chagas@ioc.fiocruz.br (B.D.d.C.); luizaper@ioc.fiocruz.br (L.d.O.R.P.); boitemc@ioc.fiocruz.br (M.C.B.)

**\*** Correspondence: elisa.cupolillo@ioc.fiocruz.br; Tel.: +55-21-38658177

**Abstract:** The description of the genus *Leishmania* as the causative agent of leishmaniasis occurred in the modern age. However, evolutionary studies suggest that the origin of *Leishmania* can be traced back to the Mesozoic era. Subsequently, during its evolutionary process, it achieved worldwide dispersion predating the breakup of the Gondwana supercontinent. It is assumed that this parasite evolved from monoxenic Trypanosomatidae. Phylogenetic studies locate dixenous *Leishmania* in a well-supported clade, in the recently named subfamily Leishmaniinae, which also includes monoxenous trypanosomatids. Virus-like particles have been reported in many species of this family. To date, several *Leishmania* species have been reported to be infected by *Leishmania* RNA virus (LRV) and *Leishbunyavirus* (LBV). Since the first descriptions of LRVs decades ago, differences in their genomic structures have been highlighted, leading to the designation of LRV1 in *L*. (*Viannia*) species and LRV2 in *L*. (*Leishmania*) species. There are strong indications that viruses that infect *Leishmania* spp. have the ability to enhance parasitic survival in humans as well as in experimental infections, through highly complex and specialized mechanisms. Phylogenetic analyses of these viruses have shown that their genomic differences correlate with the parasite species infected, suggesting a coevolutionary process. Herein, we will explore what has been described in the literature regarding the relationship between *Leishmania* and endosymbiotic *Leishmania* viruses and what is known about this association that could contribute to discussions about the worldwide dispersion of *Leishmania.*

**Keywords:** *Leishmania*; *Leishmania* viruses; phylogeny; coevolution; endosymbiont protozoan viruses
